Proangiogenic scaffolds as functional templates for cardiac tissue engineering
Proangiogenic scaffolds as functional templates for cardiac tissue engineering
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DOI：
10.1073/pnas.1006442107
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发表时间：
2010-08-24
影响因子：
11.1
通讯作者：
Ratner, Buddy D.
中科院分区：
文献类型：
--
作者：
Madden, Lauran R.;Mortisen, Derek J.;Ratner, Buddy D.
我们在这里展示了一种心脏组织工程策略，解决多细胞组织、整合到宿主心肌中以及重建心肌功能结构的方向线索。微模板技术用于将聚（甲基丙烯酸 2-羟乙酯-甲基丙烯酸）水凝胶成型为组织工程支架，其结构可驱动心脏组织整合。该结构包含组织心肌细胞束的平行通道，由微米大小的球形互连孔支撑，可增强血管生成，同时减少疤痕形成。将人 ES 细胞衍生的心肌细胞接种到表面修饰的支架上并进行体外培养。心肌细胞在支架中存活并增殖2周，达到成人心脏密度。孔径为30-40μm的无细胞支架的心脏植入显示出血管生成和纤维化反应减少，这与巨噬细胞表型向M2状态的转变相一致。这项工作通过在支架中为心肌细胞和基质提供离散的隔室，增强血管化和整合，同时控制炎症反应，为空间控制的心脏组织工程奠定了基础。
We demonstrate here a cardiac tissue-engineering strategy addressing multicellular organization, integration into host myocardium, and directional cues to reconstruct the functional architecture of heart muscle. Microtemplating is used to shape poly(2-hydroxyethyl methacrylate-co-methacrylic acid) hydrogel into a tissue-engineering scaffold with architectures driving heart tissue integration. The construct contains parallel channels to organize cardiomyocyte bundles, supported by micrometer-sized, spherical, interconnected pores that enhance angiogenesis while reducing scarring. Surface-modified scaffolds were seeded with human ES cell-derived cardiomyocytes and cultured in vitro. Cardiomyocytes survived and proliferated for 2 wk in scaffolds, reaching adult heart densities. Cardiac implantation of acellular scaffolds with pore diameters of 30-40 mu m showed angiogenesis and reduced fibrotic response, coinciding with a shift in macrophage phenotype toward the M2 state. This work establishes a foundation for spatially controlled cardiac tissue engineering by providing discrete compartments for cardiomyocytes and stroma in a scaffold that enhances vascularization and integration while controlling the inflammatory response.